BioProject

Levels of flagellin, the Toll-like receptor 5 (TLR5) ligand, are low and finely regulated in the healthy gut. More...

Levels of flagellin, the Toll-like receptor 5 (TLR5) ligand, are low and finely regulated in the healthy gut. TLR5-deficient mice (Tlr5-/-) displays metabolic syndrome driven by pro-inflammatory gut microbiota along with over-production of flagellin by a diversity of intestinal microbes. This excess flagellin production results in part from abnormally low levels of flagellin-specific antibodies. The feedback between levels of flagellin, flagellin-specific antibodies and TLR5 signaling is not well understood. Here, we show that TLR5 deficiency on non-hematopoietic cells is required and sufficient to result in greater levels of bioactive flagellin in gut that occurs without a perturbation to the microbial diversity. TLR5 deficiency promotes the differentiation of B cells into IgA-secreting plasma cells and reshapes immunoglobulin (Ig) repertoire in the large intestine. Our data show that modulating microbiota gene expression, instead of altering microbiota community, would be the target for the therapeutic design of regulating intestinal B cell responses. Less...